Variant rs231020 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000304.4(PMP22):c.178+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,544,988 control chromosomes in the GnomAD database, including 224,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27480 hom., cov: 32)

Exomes 𝑓: 0.53 ( 197514 hom. )

Consequence

PMP22
NM_000304.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

PMP22 (HGNC:9118): (peripheral myelin protein 22) This gene encodes an integral membrane protein that is a major component of myelin in the peripheral nervous system. Studies suggest two alternately used promoters drive tissue-specific expression. Various mutations of this gene are causes of Charcot-Marie-Tooth disease Type IA, Dejerine-Sottas syndrome, and hereditary neuropathy with liability to pressure palsies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

PMP22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-15259072-T-C is Benign according to our data. Variant chr17-15259072-T-C is described in ClinVar as [Benign]. Clinvar id is 633487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-15259072-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMP22	NM_000304.4 linkuse as main transcript	c.178+22A>G		intron_variant		ENST00000312280.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMP22	ENST00000312280.9 linkuse as main transcript	c.178+22A>G		intron_variant		1	NM_000304.4	P1

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89832

AN:

151976

Hom.:

27423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.701

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.592

GnomAD3 exomes

AF:

0.541

AC:

134747

AN:

249120

Hom.:

36933

AF XY:

0.535

AC XY:

72015

AN XY:

134542

show subpopulations

Gnomad AFR exome

AF:

0.762

Gnomad AMR exome

AF:

0.541

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.594

Gnomad SAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.430

Gnomad NFE exome

AF:

0.526

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

AF:

0.530

AC:

738269

AN:

1392894

Hom.:

197514

Cov.:

AF XY:

0.530

AC XY:

369255

AN XY:

697010

show subpopulations

Gnomad4 AFR exome

AF:

0.764

Gnomad4 AMR exome

AF:

0.548

Gnomad4 ASJ exome

AF:

0.560

Gnomad4 EAS exome

AF:

0.592

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.427

Gnomad4 NFE exome

AF:

0.524

Gnomad4 OTH exome

AF:

0.540

GnomAD4 genome

AF:

0.591

AC:

89940

AN:

152094

Hom.:

27480

Cov.:

AF XY:

0.586

AC XY:

43580

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.755

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.594

Gnomad4 SAS

AF:

0.528

Gnomad4 FIN

AF:

0.423

Gnomad4 NFE

AF:

0.527

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.550

Hom.:

18218

Bravo

AF:

0.609

Asia WGS

AF:

0.571

AC:

1983

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Charcot-Marie-Tooth disease, type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

Jan 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.20

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over